Differential effects of ovarian steroids on anxiety versus fear as measured by open field test and fear-potentiated startle

The ovarian steroids, estrogen (E) and progesterone (P), have been shown to affect anxiety and fear in humans and animals, although with inconsistent results. These ambiguous findings may be due to differential actions of ovarian steroids on anxiety versus fear. To investigate such a role, we used the open field test (OFT) and fear-potentiated startle (FPS). We examined these behaviors between cycling female rats in proestrus (high E and rising P) or diestrus (low E and P), as well as between ovariectomized rats treated for 2 weeks with placebo, E, or E plus P (OVX, OVX/E, OVX/EP, respectively). We found no differences in anxiety-like or fear behaviors in OFT or FPS between proestrus and diestrus rats, perhaps due to the opposing effects of E and P. In contrast, we found that the OVX/E rats spent more time in the center of the OFT compared to the OVX and OVX/EP rats with no difference in overall activity level, suggesting that E reduced anxiety and this was opposed by P. With FPS, the OVX/E rats showed increased startle in the first third of the testing session, followed by a rapid decline in startle magnitude in subsequent trials. The addition of P to E treatment counteracted this effect. In conclusion, E may have differential effects on specific components of anxiety and fear; E may decrease anxiety in a naturalistic environment, but intensify both fear learning and extinction processes. P antagonizes these E effects on anxiety and fear.